{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T20:36:19Z","timestamp":1783715779828,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DP5 OD017908"],"award-info":[{"award-number":["DP5 OD017908"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009670","name":"National Alliance for Research on Schizophrenia and Depression","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009670","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003194","name":"New York Stem Cell Foundation","doi-asserted-by":"publisher","award":["NYSTEM C\u2010029157"],"award-info":[{"award-number":["NYSTEM C\u2010029157"]}],"id":[{"id":"10.13039\/100003194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","award":["NARSAD Young Investigator Grant"],"award-info":[{"award-number":["NARSAD Young Investigator Grant"]}],"id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006474","name":"Columbia University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006474","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hippocampus"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent genetic tools have allowed researchers to visualize and manipulate memory traces (i.e., engrams) in small brain regions. However, the ultimate goal is to visualize memory traces across the entire brain in order to better understand how memories are stored in neural networks and how multiple memories may coexist. Intact tissue clearing and imaging is a new and rapidly growing area of focus that could accomplish this task. Here, we utilized the leading protocols for whole\u2010brain clearing and applied them to the ArcCreER<jats:sup>T2<\/jats:sup> mice, a murine line that allows for the indelible labeling of memory traces. We found that CLARITY and PACT greatly distorted the tissue, and iDISCO quenched enhanced yellow fluorescent protein (EYFP) fluorescence and hindered immunolabeling. Alternative clearing solutions, such as tert\u2010Butanol, circumvented these harmful effects, but still did not permit whole\u2010brain immunolabeling. CUBIC and CUBIC with Reagent\u20101A produced improved antibody penetration and preserved EYFP fluorescence, but also did not allow for whole\u2010brain memory trace visualization. Modification of CUBIC with Reagent\u20101A resulted in EYFP fluorescence preservation and immunolabeling of the immediate early gene (IEG) Arc in deep brain areas; however, optimized memory trace labeling still required tissue slicing into mm\u2010thick tissue sections. In summary, our data show that CUBIC with Reagent\u20101A* is the ideal method for reproducible clearing and immunolabeling for the visualization of memory traces in mm\u2010thick tissue sections from ArcCreER<jats:sup>T2<\/jats:sup> mice.<\/jats:p>","DOI":"10.1002\/hipo.22951","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T01:01:50Z","timestamp":1523926910000},"page":"523-535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Optimization of immunolabeling and clearing techniques for indelibly labeled memory traces"],"prefix":"10.1002","volume":"28","author":[{"given":"Ina P.","family":"Pavlova","sequence":"first","affiliation":[{"name":"Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. (RFMH)\/New York State Psychiatric Institute (NYSPI) New York New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon C.","family":"Shipley","sequence":"additional","affiliation":[{"name":"Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. (RFMH)\/New York State Psychiatric Institute (NYSPI) New York New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Lanio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, MD\u2010PhD Program College of Physicians and Surgeons, Columbia University Medical Center New York New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Hen","sequence":"additional","affiliation":[{"name":"Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. (RFMH)\/New York State Psychiatric Institute (NYSPI) New York New York 10032"},{"name":"Department of Psychiatry Columbia University New York New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6926-2020","authenticated-orcid":false,"given":"Christine A.","family":"Denny","sequence":"additional","affiliation":[{"name":"Division of Integrative Neuroscience Research Foundation for Mental Hygiene, Inc. (RFMH)\/New York State Psychiatric Institute (NYSPI) New York New York 10032"},{"name":"Department of Psychiatry Columbia University New York New York 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.037"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22155"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22556"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12107"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.018"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0022-15.2015"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.119"},{"key":"e_1_2_6_9_1","first-page":"1","article-title":"Imaging cleared intact biological systems at a cellular level by 3DISCO","volume":"89","author":"Ert\u00fcrk A.","year":"2014","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3170"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4107"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2928"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1016\/S0021-9258(18)63111-4","article-title":"On the structural stability denaturation of proteins","volume":"245","author":"Herskovits T. 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